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Preventive Therapy for Contacts of Drug-Resistant Tuberculosis.

ABSTRACT: Preventing the progression of a drug-resistant tuberculosis (DR-TB) infection to disease is an important pillar of the DR-TB elimination strategy. International guidelines have recently proposed fluoroquinolones for tuberculosis preventive therapy (TPT) in DR-TB contacts, although the available evidence is low quality. The pooled data from small observational studies suggest that a fluoroquinolone-based TPT is safe, effective and cost-effective as a preventive treatment in DR-TB contacts. Three clinical trials are currently ongoing to generate higher quality evidence on the efficacy of levofloxacin and delamanid as a DR-TB preventive therapy. Additional evidence is also needed, regarding TPT treatment in fluoroquinolone-resistant-TB contacts, patient and health care worker perceptions on DR-TB preventive therapy for contacts, and the service delivery models to increase DR-TPT access. This state-of-the-art review presents the current literature on TPT for contacts of DR-TB cases, focusing on the available evidence and international guidelines.

SUBMITTER: Kherabi Y

PROVIDER: S-EPMC9609446 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Preventive Therapy for Contacts of Drug-Resistant Tuberculosis.

Kherabi Yousra Y Tunesi Simone S Kay Alexander A Guglielmetti Lorenzo L

Pathogens (Basel, Switzerland) 20221015 10

Preventing the progression of a drug-resistant tuberculosis (DR-TB) infection to disease is an important pillar of the DR-TB elimination strategy. International guidelines have recently proposed fluoroquinolones for tuberculosis preventive therapy (TPT) in DR-TB contacts, although the available evidence is low quality. The pooled data from small observational studies suggest that a fluoroquinolone-based TPT is safe, effective and cost-effective as a preventive treatment in DR-TB contacts. Three ...[more]

PMID: 36297246

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Project description:The World Health Organization (WHO) recently changed its guidance for tuberculosis (TB) preventive treatment (TPT) recommending TPT for all pulmonary TB (PTB) exposed household contacts (HHC) to prevent incident TB disease (iTBD), regardless of TB infection (TBI) status. However, this recommendation was conditional as the strength of evidence was not strong. We assessed risk factors for iTBD in recently-exposed adult and pediatric Indian HHC, to determine which HHC subgroups might benefit most from TPT. We prospectively enrolled consenting HHC of adult PTB patients in Pune and Chennai, India. They underwent clinical, microbiologic and radiologic screening for TB disease (TBD) and TBI, at enrollment, 4-6, 12 and 24 months. TBI testing was performed by tuberculin skin test (TST) and Quantiferon®- Gold-in-Tube (QGIT) assay. HHC without baseline TBD were followed for development of iTBI and iTBD. Using mixed-effect Poisson regression, we assessed baseline characteristics including TBI status, and incident TBI (iTBI) using several TST and/or QGIT cut-offs, as potential risk factors for iTBD. Of 1051 HHC enrolled, 42 (4%) with baseline TBD and 12 (1%) with no baseline TBI test available, were excluded. Of the remaining 997 HHC, 707 (71%) had baseline TBI (TST #x2265; 5 mm or QGIT #x2265; 0.35 IU/ml). Overall, 20 HHC (2%) developed iTBD (12 cases/1000 person-years, 95%CI: 8-19). HIV infection (aIRR = 29.08, 95% CI: 2.38-355.77, p = 0.01) and undernutrition (aIRR = 6.16, 95% CI: 1.89-20.03, p = 0.003) were independently associated with iTBD. iTBD was not associated with age, diabetes mellitus, smoking, alcohol, and baseline TBI, or iTBI, regardless of TST (#x2265; 5 mm, #x2265; 10 mm, #x2265; 6 mm increase) or QGIT (#x2265; 0.35 IU/ml, #x2265; 0.7 IU/ml) cut-offs. Given the high overall risk of iTBD among recently exposed HHCs, and the lack of association between TBI status and iTBD, our findings support the new WHO recommendation to offer TPT to all HHC of PTB patients residing in a high TB burden country such as India, and do not suggest any benefit of TBI testing at baseline or during follow-up to risk stratify recently-exposed HHC for TPT.

Dataset Information

Preventive Therapy for Contacts of Drug-Resistant Tuberculosis.

Publications

Preventive Therapy for Contacts of Drug-Resistant Tuberculosis.

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